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Is there a genetic reason many of us do lousy on T4?

deiodinase2Last May, a very inte­res­ting article appea­red in the May 2009 issue of the Jour­nal of Cli­ni­cal Endoc­ri­no­logy and Meta­bo­lism, tit­led For Some, L-Thyroxine Repla­ce­ment Might Not Be Enough: A Gene­tic Ratio­nale and pre­sen­ted by Endoc­ri­no­lo­gists in Bris­tol in the UK. It’s accom­pa­nied with an edi­to­rial by Endoc­ri­no­lo­gists Brian W. Kim and Anto­nio C. Bianco.

This is the same article refe­rred to by Endoc­ri­no­lo­gist Dr. Gary Pep­per on the last Thy­roid Patient Com­mu­nity Call on Talkshoe.

Basi­cally, the article sta­tes that a gene­tic varia­tion in the enzyme that con­verts T4 to T3, deio­di­nase D2 (also called Type 2 Deio­di­nase, or 5′-Deiodinase), may be res­pon­si­ble for why so many thy­roid patients don’t do well on Synth­roid, Levoxyl, levothy­ro­xine, etc, and in turn, do so much bet­ter on natu­ral desic­ca­ted thy­roid like Natu­reth­roid, Erfa’s Thy­roid, or the com­bi­ned synthe­tic T4 and synthe­tic T3 (Cytomel).

In other words, where some may have a strongly func­tio­ning deio­di­nase D2 enzyme which con­verts T4 to the active T3 well, others may have a modi­fied deio­di­nase D2 enzyme, cau­sing less opti­mal conversion.

In the Edi­to­rial, the two Endos Kim and Bianco explain the rea­lity of “polymorphism” – a con­di­tion in nature in which chan­ges or varia­tions occur, and in one patient from another, a change in the DNA.  As rela­ted to con­ver­sion of T4 to T3,  some thy­roid patients have a less effec­tive deio­di­nase D2 enzyme in the con­ver­sion of T4 to T3.  Spe­ci­fi­cally, there is a com­mon variant of the gene, threo­nine (Thr) 92 ala­nine (Ala), and it results in dec­rea­sed D2 enzy­ma­tic activity.

The study pro­po­ses that this alte­ra­tion from poly­morphism occurs in 16% of those stu­died, and conc­lu­des that the majo­rity don’t have this pro­blem, and thus, “most do fine on T4-only medi­ca­tions”. But 16% do have this pro­blem and need the com­bi­ned the­rapy of T4 with T3.

Bris­tol was also men­tio­ning this rea­lity in 2004 here, even if they thought it was as low as 5%.

As Dr. Pep­per hin­ted, this study could do won­ders to open the eyes of Endoc­ri­no­lo­gists about the use of desic­ca­ted thy­roid, or at the very least, about com­bi­ned hypothy­roid treat­ment with synthe­tic T3 added to synthe­tic T4.  And I’m glad for that when so many patients have found Endoc­ri­no­lo­gists to be narrow-mindedly stuck on Synth­roid or other T4-only thy­ro­xine products.

Of course, infor­med thy­roid patients know this is only a baby step in the right direc­tion, even if a good one! So we’ll rejoice for this study, and watch for more pro­gress from the medi­cal com­mu­nity and Endoc­ri­no­logy in gene­ral. For exam­ple, saying that “most do fine on T4” simply because they have may a non-variation might be pro­ven wrong as phy­si­cians take the time to really look at those “fine” patients, espe­cially as they age and symp­toms of an infe­rior treat­ment do pop up. And though the com­bi­na­tion of synthe­tic T3 with synthe­tic T4 defi­ni­tely gives bet­ter results, thy­roid patients who then moved to desic­ca­ted thy­roid with it’s T4, T3, T2, T1 and cal­ci­to­nin report even bet­ter results and cli­ni­cal pre­sen­ta­tion!  We’ve also lear­ned that the TSH lab test abso­lu­tely sucks when it comes to diag­no­sis and treat­ment.  Read TSH Why It’s Use­less, or see even more detail in Chap­ter Four of the STTM book, tit­led Thy­roid Sti­mu­la­ting Hooey.

And finally: do thy­roid patients really believe that pro­blems with T4-only treat­ment is simply due to a gene­tic abnor­ma­lity or varia­tion? Maybe. But isn’t it funny that a healthy human thy­roid does NOT depend solely on con­ver­sion, but also gives direct T3. hmmmmmm

P.S.  Patients also know that the use of the sup­ple­ment Sele­nium helps with con­ver­sion, by the way, but has never stop­ped our first-hand know­ledge that desic­ca­ted thy­roid rocks!


  • Want to keep track of these “fringe web­site” blog posts? ;-) Curious what’s on Janie’s mind? Use the noti­fi­ca­tion on the lower left of the links, called a News­let­ter, or an RSS Feed.
  • The extre­mely hip and sophis­ti­ca­ted STTM t-shirts are half price! Great BUMPER STICKERS, too. Spread the word – YOU may make a dif­fe­rence in someone’s life.
  • Check out the patient-to-patient book with even more detail (and which doc­tors seem to res­pect more than websites).
  • Need to unders­tand all your best options for thy­roid treat­ment? Go here.
  • Keep infor­med of each live Thy­roid Patient Com­mu­nity Call on Talkshoe by sig­ning up as a follo­wer.

Thyroid patients report despising their Endocrinologists — but here’s one you might just love!

officedoor2

I once crac­ked open an egg to find it had TWO shells.  And that oddity is equi­va­lent to fin­ding an Endoc­ri­no­lo­gist who sup­ports the use of natu­ral desic­ca­ted thy­roid. 

Voila!! ~~ you can lis­ten and talk to an Endo who does just that on this Thurs­day evening’s popu­lar THYROID PATIENT COMMUNITY CALL on TalkShoe.

His name is Dr. Gary Pep­per, Board Cer­ti­fied by the Ame­ri­can Boards of Inter­nal Medi­cine, and Endoc­ri­no­logy and Meta­bo­lism and editor-in-chief of metabolism.com.  Besi­des ser­ving many years in dis­tin­guished lea­dership posi­tions, he was selec­ted as one of the top 100 phy­si­cians in New York City by New York Maga­zine and is also a fea­tu­red expert with CNBC and ivi­llage on topics of dia­be­tes and endoc­ri­no­logy. He sta­tes:  Almost daily I reread the words of Sir William Osler: “It’s often more impor­tant to know what sort of per­son this disease has than to know what disease the per­son has.”

i.e. this is one of a rare but gro­wing breed of doc­tors who sup­ports what we as thy­roid patients already know – that desic­ca­ted thy­roid is a five-star hypothy­roid treat­ment and T4-only is about as effec­tive as a dough­nut diet for most. And lo and behold,  Dr. Pep­per is an Endoc­ri­no­lo­gist! Of course, I can give no gua­ran­tees how he is as a doc­tor in his own office, but I do appre­ciate his unders­tan­ding that T4-only treat­ment may not be the best way to treat hypo.

Join us this Thurs­day eve­ning, 6 pm Paci­fic, 7 pm Moun­tain, 8 pm Cen­tral and 9 pm Eas­tern by clic­king on the first link above tit­led Thy­roid Patient Com­mu­nity Call.  When on that page, you’ll also see the exact day and time left before the call. You’ll be able to lis­ten to the call right on your com­pu­ter, or you can dial in and lis­ten on your phone. There is also an option to talk one-on-one live with Dr. Pep­per and Janie.

And remem­ber: neither I or Dr. Pep­per can offer per­so­nal medi­cal advice or pro­vide indi­vi­dual spe­ci­fic coun­se­ling. Those are bet­ween you and your per­so­nal phy­si­cian.

***P.S.  Phar­ma­Ti­mes this month repor­ted that this quarter’s sales of  Synth­roid (levothy­ro­xine) were up 3.7% to $134 million by Abbott Labs. Sad for most of those patients. If you know of someone who has been put on a T4 med, send them here: www.stopthethyroidmadness.com/t4-only-meds-dont-work or to the audio page here: www.stopthethyroidmadness.com/audio-shorts (third one down).


  • Want to keep track of these “fringe web­site” blog posts? ;-) Curious what’s on Janie’s mind? Use the noti­fi­ca­tion on the lower left of the links, called a News­let­ter, or an RSS Feed.
  • The extre­mely hip and sophis­ti­ca­ted STTM t-shirts are half price! Great BUMPER STICKERS, too. Spread the word – YOU may make a dif­fe­rence in someone’s life.
  • Check out the patient-to-patient book with even more detail (and which doc­tors seem to res­pect more than websites).
  • Need to unders­tand all your best options for thy­roid treat­ment? Go here.
  • Keep infor­med of each live Thy­roid Patient Com­mu­nity Call on Talkshoe by sig­ning up as a follo­wer.
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